Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study

Abstract

Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture in etiology, which has not been comprehensively investigated. In this study, we leveraged summary-level data from the latest COVID-19 host genetics consortium and UK Biobank to study the genetic commonality between COVID-19 traits and VTE. We found a positive genetic correlation between COVID-19 hospitalization and VTE (rg = 0.2320, P-value= 0.0092). The cross-trait analysis identified shared genetic loci between VTE and COVID-19 traits, including 8 for severe COVID-19, 11 for COVID-19 hospitalization, and 7 for SARS-CoV-2 infection. We identified seven novel mapped genes (LINC00970, TSPAN15, ADAMTS13, F5, DNAJB4, SLC39A8 and OBSCN) that were enriched for expression in the lung tissue, and in coagulation and immune related pathways. Eight genetic loci were found to share causal variants between COVID-19 and VTE, which are localized in the ABO, ADAMTS13 and FUT2 gene regions. Bi-directional Mendelian randomization analysis did not suggest a causal relationship between VTE and COVID-19 traits. Our study advances the understanding of shared genetic etiology of COVID-19 and VTE at the molecular and functional levels.

Causal Association Between Peripheral blood immune cells and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

“…A 'leave one out' analysis was conducted to assess the in uence of individual SNPs on the exposure-outcome relationship, with a p-value over 0.05 signifying no horizontal pleiotropy [29] . To clarify whether the immune cell traits and RA genetically share the same genetic variant, we performed gene colocalization analysis [30] . To mitigate false positives in multiple testing, false discovery rate (FDR) correction was applied.…”

Strength of Anticoagulation in Moderate to Severe COVID-19 Illness: In Medio Stat Virtus?

“…25 Interestingly, another preprint cross-trait analysis published by Huang et al found that VTE shared as many as eight and eleven genetic loci with severe SARS-CoV-2 infection and hospitalization for COVID-19, including genes participating to blood coagulation (e.g., ADAMTS-13 [a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] and FV ). 26…”

“…25 Interestingly, another preprint cross-trait analysis published by Huang et al found that VTE shared as many as eight and eleven genetic loci with severe SARS-CoV-2 infection and hospitalization for COVID-19, including genes participating to blood coagulation (e.g., ADAMTS-13 [a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13] and FV). 26 The evidence emerged so far would hence persuade us that, perhaps, the most reasonable approach is not a matter of whether therapeutic-intensity anticoagulation may be "good" or "bad," "safe," or "dangerous," in patients with severe COVID-19 illness, but rather whether the correct answer to the original question could be… "depends." Straightforwardly applying here the concept of precision medicine, one would need to estimate the individual risk of developing venous thrombosis (i.e., as from elements summarized in ►Table 1), 27,28 that would then be balanced against the risk of bleeding.…”